Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-2 (IL-2) production was studied in T lymphocytes from 32 patients with systemic lupus erythematosus (SLE) and 27 healthy volunteers. The IL-2 production by phytohemagglutinin (PHA)-stimulated cells from SLE patients was significantly depressed compared to control values, with a correlation between degree of depression and disease activity. The depressed IL-2 production by SLE T cells are largely reversed by the addition of either phorbol ester (PMA) or partially by a calcium ionophore. SLE T cells had significantly lower peak increases in intracellular free calcium [( Ca2+]i) than controls after stimulation by PHA or by a monoclonal antibody against the CD3 antigen. This abnormality was found even in T cells from patients with mild disease activity or in those whose T cells produced normal amounts of IL-2. Calcium ionophore produced similar increases in [Ca2+]i in SLE patients as in normals. These results suggest that a major component of the defect responsible for decreased IL-2 production by SLE lymphocytes is proximal to protein kinase C activation and may involve impaired signal transduction after activation of the antigen receptor complex.
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PMID:Impaired T-cell activation in patients with systemic lupus erythematosus. 251 25

Intracellular recording from hippocampal CA1 pyramidal cells was used to characterize the pharmacological properties of muscarinic responses. Results obtained with the M1 antagonist pirenzepine and the M2 antagonist gallamine suggest that an M1 muscarinic receptor is involved in the muscarinic-induced membrane depolarization and blockade of the afterhyperpolarization (AHP). On the other hand, an M2 receptor may be involved in the cholinergic depression of the EPSP and the blockade of the potassium current termed the M-current. Pretreatment of hippocampi with pertussis toxin did not prevent any of the muscarinic responses suggesting that a pertussis toxin-sensitive G-protein is not involved. The M-current, in contrast to the other muscarinic actions, was unaffected by muscarinic agonists which are weak at increasing phosphoinositide (PI) turnover and actually blocked the action of full agonists. This finding suggests that stimulation of PI turnover may be involved in the blockade of the M-current. Although activation of protein kinase C with phorbol esters has little effect on the M-current, intracellular application of inositol trisphosphate did reduce the M-current. We were unable to establish any clear relationship between biochemical effector systems and the muscarinic receptor subtypes.
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PMID:Pharmacological characterization of muscarinic responses in rat hippocampal pyramidal cells. 253 6

Angiogenin transiently depresses the cAMP level of rat aortic smooth muscle cells. The dose response is similar to angiogenin activation of the inositol-specific phospholipase C in this cell line [Moore, F. & Riordan, J.F. (1989) Biochemistry. Submitted]. The time course showed a maximal depression (28%) in cAMP at 2 min, followed by a return to that of unstimulated cells by 3.5 min. Angiogenin also inhibited isoproterenol stimulated cAMP formation, but the percentage depression in cAMP (9%) was less than that in cells treated with angiogenin alone (28%). In contrast angiogenin enhanced forskolin stimulation of adenylate cyclase, an effect previously linked with agonist activation of protein kinase C. The effect of angiogenin on cellular cAMP was abolished by pre-incubation with pertussis toxin. Angiogenin had no effect on cellular cGMP. These results are consistent with activation of adenylate cyclase Gi following exposure of the cells to angiogenin and provide further evidence for interaction between cellular signalling pathways.
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PMID:Angiogenin depresses aortic smooth muscle cell cAMP by a pertussis toxin sensitive mechanism. 255 Dec 76

The present study evaluated whether protein kinase C (PKC) activation was involved in the lymphocytosis promoting properties of pertussis toxin (Ptx). The exposure of mouse lymphocytes to phorbol esters (as a means to selectively activate PKC) caused a depression in their subsequent capacity to localize into lymph nodes and Peyer's patches in vivo. This pattern of inhibition was quite similar to that observed with lymphocytes treated with Ptx. The mechanisms responsible for the observed decreases in localization to lymphoid organs caused by these two agents, however, appeared to be distinct. Exposure of lymphocytes to PMA was followed by a time and dosage-dependent decrease in the surface density of MEL-14 defined homing receptors. Ptx-treated lymphocytes retained normal density of this homing receptor. Consequently, PMA-treated lymphocytes lost their capacity to bind to high-endothelial venules in in vitro lymph node binding assays while Ptx-treated cells retained normal high-endothelial venule binding potential. We conclude from this study that: 1) the activation of PKC in lymphocytes by PMA can alter their recirculation properties via mechanisms that diminish their expression of surface receptors which support extravasation into lymph node and mucosal lymphoid tissues, and 2) even though Ptx has been reported to elevate the rate of inositol phosphate turnover in lymphocytes, the loss of extravasation potential of Ptx-treated lymphocytes is not mediated via the modification of surface homing receptors as observed in cells exposed to the known PKC activator, PMA.
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PMID:Molecular mechanisms of lymphocyte extravasation. III. The loss of lymphocyte extravasation potential induced by pertussis toxin is not mediated via the activation of protein kinase C. 273 69

A depression in aortic contractility has been previously demonstrated in rat intraperitoneal sepsis and during endotoxemia. In this study, we determined whether the mobilization of extracellular calcium (using 45Ca) and the release of intracellular calcium are altered in septic rat aorta when compared to sham-operated controls. The concentration of protein kinase C was also determined by using [3H] phorbol-12,13-dibutyrate (PDBu). We found that calcium influx was unaltered under basal conditions but that the ability of norepinephrine (NE) to augment influx was significantly depressed (P less than .05; [control vs. septic, 572 +/- 54 [SE] vs. 428 +/- 30 mumol Ca2+/kg dry wt. aorta]). Calcium influx stimulated by high K+ was unchanged in aortae between control and septic animals. In the presence of NE, calcium efflux (an indirect measurement of intracellular calcium release) was significantly diminished (P less than .001) in aortae from septic rats. The concentration of aortic protein kinase C as assessed by PDBu binding sites was unaltered in septic rats when compared with controls. In conclusion, we found that during sepsis alpha 1-adrenergic receptor activation of both calcium influx and efflux by NE is decreased; these alterations could be related to the depressed aortic contractility observed in sepsis.
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PMID:Alterations in bidirectional transmembrane calcium flux occur without changes in protein kinase C levels in rat aorta during sepsis. 283 8

Pharmacological properties of pre- and postsynaptic GABAB receptors were compared in CA1 hippocampal pyramidal neurons in vitro. The postsynaptic effects mediated by GABAB receptors, i.e., the baclofen-induced hyperpolarization, the bicuculline-resistant GABA response, and the slow inhibitory postsynaptic potential elicited by CA1 afferent stimulation, are all blocked by pertussis toxin (which inactivates some G proteins). These events are also suppressed by stimulating protein kinase C by phorbol esters and blocked by the selective GABAB antagonist phaclofen. In contrast, the baclofen-induced presynaptic depression of the excitatory postsynaptic potential elicited by CA1 afferent stimulation is resistant to the action of pertussis toxin and is not antagonized by phaclofen. However, this presynaptic inhibition can be antagonized by phorbol esters. These results indicate that the pre- and postsynaptic effects mediated by GABAB receptors in hippocampus have distinctly different pharmacological properties and possibly a different coupling mechanism.
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PMID:Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. 285 99

Cyclic GMP depresses Ba2+ current through high-voltage-activated Ca2+ channels (ICa) in acutely isolated hippocampal neurons. The effect is produced by intra-, but not extracellular, cGMP or by 5' GMP. The membrane-permeant derivative, 8-Br-cGMP, produces a reversible suppression. The effect of 8-Br-cGMP is similar to phorbol ester-induced ICa depression, except that ICa depression due to 8-Br-cGMP is not blocked by protein kinase inhibitors H-8 or H-7, whereas phorbol ester effects are. The data suggest that cGMP depresses ICa by a cGMP-kinase- and protein kinase C (PKC)-independent mechanism. Cyclic AMP, which enhances ICa, and the cyclic nucleotide phosphodiesterase inhibitor, IBMX, both antagonize ICa depression induced by 8-Br-cGMP, but not that due to phorbol esters. Cyclic IMP, a more potent activator of phosphodiesterase than of cGMP-dependent protein kinase, is also a powerful depressant of ICa. We conclude that cGMP-induced depression of ICa is mediated by activation of cyclic nucleotide phosphodiesterase with consequent reduction of intracellular cAMP.
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PMID:Cyclic GMP depresses hippocampal Ca2+ current through a mechanism independent of cGMP-dependent protein kinase. 285 1

In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity.
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PMID:Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study. 290 1

Diacylglycerol analogues (for example 1,2-oleoylacetylglycerol, OAG) and phorbol esters are activators of protein kinase C, and have been widely used to study the function of this enzyme in both intact cells and cell-free preparations. Electrophysiological studies have shown that these activators can either depress or increase Ca2+ currents, or decrease K+ currents when applied outside the cell. It has been assumed that these effects are mediated by protein kinase C activation. Here we report that micromolar levels of OAG and phorbol esters depress Ca2+ currents in chick sensory neurons independently of their effect as activators of protein kinase C. The depression of the Ca2+ current is rapid and is unaffected by intracellular application of the protein kinase C inhibitors staurosporin, sphingosine and H-7. Furthermore, the activators were ineffective when applied intracellularly, indicating that their site of action is on the outside of the membrane.
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PMID:A diacylglycerol analogue reduces neuronal calcium currents independently of protein kinase C activation. 292 62

Previous studies on the regulation of responses of neutrophils to fMet-Leu-Phe have demonstrated the relevance of the role of the rate of occupation of the receptors by the stimulant. When this rate is decreased by presenting the peptide to neutrophils over a period of time by means of an infusion pump, the activation of the respiratory burst and of the secretion is greatly depressed or is absent. This paper deals with further investigations on the mechanisms of this desensitization, which previous results have shown to consist of an uncoupling between the ligand-receptor complexes and the target for cell responses, caused by the deceleration of the initial rate of occupation of the receptors. The data presented here demonstrate that this desensitization is not linked to the formation of a negative intermediate such as cAMP, but is associated with: (i) a depression of the rate and magnitude of the phosphatidylinositol response (activation of phosphatidylinositol turnover measured as modification of incorporation of [32P]Pi and [3H]glycerol into phosphatidylinositol and phosphatidic acid); (ii) a deceleration of the rate of the release of bound Ca2+, without a decrease in the total quantity of Ca2+ liberated (measured as fluorescence changes of chlorotetracycline treated neutrophils); (iii) a slower rise of cytosolic free Ca2+ concentration [Ca2+]i, without a decrease in the magnitude of the final increase of [Ca2+]i (monitored with Quin 2). These findings, which are discussed in relation to the recent hypotheses on the transduction reactions of receptor-mediated stimuli for neutrophil responses, are consistent with a mechanism of desensitization involving decreased production of diacylglycerol by the hydrolysis of phosphatidylinositol and deficient activation of Ca2+-phospholipid-dependent protein kinase C.
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PMID:Mechanism of desensitization of neutrophil response to N-formylmethionylleucylphenylalanine by slow rate of receptor occupancy. Studies on changes in Ca2+ concentration and phosphatidylinositol turnover. 298 66


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